Physiological concentrations of 17beta-estradiol inhibit the synthesis of nitric oxide synthase in macrophages via a receptor-mediated system.
We investigated the effect of estrogen on inducible nitric oxide synthase (iNOS), which is not well understood, in contrast to the known effect of estrogen on endothelial nitric oxide synthase (eNOS). When J774 cells, a murine macrophage cell line, were incubated with interferon-gamma and lipopolysaccharide, iNOS was induced, and a large amount of NO was released. Pre- or coincubation with 17beta-estradiol inhibited this induction of iNOS protein and NO release; however, 17beta-estradiol did not have a direct effect on enzyme activity of iNOS. The analog, 17alpha-estradiol, did not have such an effect. Tamoxifen, an antiestrogen, and ICI182780, an estrogen-receptor antagonist, inhibited the influence of 17beta-estradiol on iNOS. Thus 17beta-estradiol inhibited the induction of iNOS by a classic receptor-mediated pathway. The inhibition of the NO release from iNOS by 17beta-estradiol is in contrast to the reported augmentation of continuous NO release from eNOS. These harmonious effects of estrogen on iNOS and eNOS may have some role in the antiatherosclerotic effects of 17beta-estradiol.
Hayashi
T
T
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Yamada
K
K
Esaki
T
T
Muto
E
E
Chaudhuri
G
G
Iguchi
A
A
D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002460:Cell Line; D004492:Edetic Acid / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D000077267:Fulvestrant; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008839:Microelectrodes; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D004965:Estrogen Antagonists; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D013629:Tamoxifen; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D007371:Interferon-gamma; D004492:Edetic Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse